Bian Fenlan, Ni Shiyao, Zhao Peng, Qi Maonanxing, Tang Bi, Wang Hongju, Kang Pinfang, Liu Jinjun
Department of Cardiology , First Affiliated Hospital of Bengbu MedicalUniversity, Bengbu 233000, China.
Key Laboratory of Cardio-Cerebrovascular Foundation and Clinical Sciences of Bengbu MedicalUniversity, Bengbu 233000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2025 May 20;45(5):977-985. doi: 10.12122/j.issn.1673-4254.2025.05.10.
To study the mechanism mediating the protective effect of asiaticoside (AS) against myocardial ischemia-reperfusion injury (MIRI) in rats.
Fifty SD rats were randomized into sham-operated group, MIRI model group and AS treatment group. AS treatment was administered at low, moderate and high doses by daily gavage for 2 weeks before MIRI modeling (n=10). Serum levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), interleukin-18 (IL-18) and IL-1β, the volume of myocardial infarction and ischemia, and myocardial pathologies of the rats were determined or observed. The protein expression levels of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the myocardial tissues were detected using Western blotting. The changes in the expression levels of these proteins were also detected in H9C2 cells with AS pretreatment prior to hypoxia-reoxygenation (H/R) injury.
The rats models of MIRI exhibited significant myocardial infarction and ischemia with increased serum levels of LDH and CK-MB and myocardial expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. AS pretreatment effectively reduced myocardial infarction volume in the rat models and significantly reduced serum LDH and CK-MB levels and the protein levels in the myocardial tissue in a dose-dependent manner. In the H9C2 cell model of H/R injury, AS pretreatment significantly suppressed the elevation of the protein expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. Molecular docking studies showed that AS had a strong binding affinity with NLRP3.
Asiaticoside can alleviate MIRI in rats possibly by inhibiting NLRP3 inflammasome-mediated pyroptosis.
研究积雪草苷（AS）对大鼠心肌缺血再灌注损伤（MIRI）保护作用的介导机制。
将50只SD大鼠随机分为假手术组、MIRI模型组和AS治疗组。在MIRI建模前2周，通过每日灌胃给予低、中、高剂量的AS（n = 10）。测定或观察大鼠血清乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）、白细胞介素-18（IL-18）和IL-1β水平、心肌梗死和缺血体积以及心肌病理学。采用蛋白质印迹法检测心肌组织中NLRP3、ASC、半胱天冬酶-1、GSDMD、GSDMD-N、IL-1β和IL-18的蛋白表达水平。在缺氧复氧（H/R）损伤前用AS预处理的H9C2细胞中，也检测这些蛋白表达水平的变化。
MIRI大鼠模型表现出明显的心肌梗死和缺血，血清LDH和CK-MB水平升高，心肌中NLRP3、ASC、半胱天冬酶-1、GSDMD、GSDMD-N、IL-1β和IL-18表达增加。AS预处理有效降低了大鼠模型的心肌梗死体积，并以剂量依赖的方式显著降低了血清LDH和CK-MB水平以及心肌组织中的蛋白水平。在H/R损伤的H9C2细胞模型中，AS预处理显著抑制了NLRP3、ASC、半胱天冬酶-1、GSDMD、GSDMD-N、IL-1β和IL-18蛋白表达的升高。分子对接研究表明，AS与NLRP3具有很强的结合亲和力。
积雪草苷可能通过抑制NLRP3炎性小体介导的细胞焦亡减轻大鼠MIRI。
